Impact of phenylalanine on cognitive, cerebral, and neurometabolic parameters in adult patients with phenylketonuria (the PICO study): a randomized, placebo-controlled, crossover, noninferiority trial

Autor: Lenka Bosanska, Christian Rummel, Roland Kreis, Roman Trepp, Regula Everts, Michel Hochuli, Raphaela Muri, Stephanie Abgottspon, Johannes Slotboom
Přispěvatelé: University of Zurich, Everts, Regula
Rok vydání: 2020
Předmět:
Male
Pediatrics
10265 Clinic for Endocrinology and Diabetology
Administration
Oral
Medicine (miscellaneous)
Clinical Trials
Phase IV as Topic
Neuropsychological Tests
Placebos
Study Protocol
Cognition
0302 clinical medicine
Phenylketonurias
2736 Pharmacology (medical)
Phenylketonuria
Pharmacology (medical)
Randomized Controlled Trials as Topic
lcsh:R5-920
0303 health sciences
education.field_of_study
Cross-Over Studies
030305 genetics & heredity
Neuropsychology
Brain
2701 Medicine (miscellaneous)
Magnetic Resonance Imaging
3. Good health
Memory
Short-Term
Treatment Outcome
PKU
Female
lcsh:Medicine (General)
Switzerland
Adult
medicine.medical_specialty
Blinding
Randomization
Phenylalanine
Population
610 Medicine & health
Neuroimaging
Equivalence Trials as Topic
Placebo
Drug Administration Schedule
03 medical and health sciences
Double-Blind Method
medicine
Humans
Effects of sleep deprivation on cognitive performance
education
Newborn screening
business.industry
Working memory
Correction
Diet
Clinical trial
business
030217 neurology & neurosurgery
Zdroj: Trials, Vol 21, Iss 1, Pp 1-11 (2020)
Trials
Trepp, Roman; Muri, Raphaela; Abgottspon, Stephanie; Bosanska, Lenka; Hochuli, Michel; Slotboom, Johannes; Rummel, Christian; Kreis, Roland; Everts, Regula (2020). Impact of phenylalanine on cognitive, cerebral, and neurometabolic parameters in adult patients with phenylketonuria (the PICO study): a randomized, placebo-controlled, crossover, noninferiority trial. Trials, 21(1), p. 178. BioMed Central 10.1186/s13063-019-4022-z
ISSN: 1745-6215
Popis: BackgroundThe population of adult patients with early-treated phenylketonuria (PKU) following newborn screening is growing substantially. The ideal target range of blood phenylalanine (Phe) levels in adults outside pregnancy is a matter of debate. Therefore, prospective intervention studies are needed to evaluate the effects of an elevated Phe concentration on cognition and structural, functional, and neurometabolic parameters of the brain.MethodsThe PICO (Phenylalanine and Its Impact on Cognition) Study evaluates the effect of a 4-week Phe load on cognition and cerebral parameters in adults with early-treated PKU in a double-blind, randomized, placebo-controlled, crossover, noninferiority trial.ParticipantsThirty adult patients with early-treated PKU and 30 healthy controls comparable to patients with regard to age, sex, and educational level will be recruited from the University Hospitals Bern and Zurich, Switzerland. Patients are eligible for the study if they are 18 years of age or older and had PKU diagnosed after a positive newborn screening and were treated with a Phe-restricted diet starting within the first 30 days of life.Intervention: The cross-over intervention consists of 4-week oral Phe or placebo administration in patients with PKU. The study design mimics a Phe-restricted and a Phe-unrestricted diet using a double-blinded, placebo-controlled approach.ObjectivesThe primary objective of the PICO Study is to prospectively assess whether a temporarily elevated Phe level influences cognitive performance (working memory assessed with a n-back task) in adults with early-treated PKU. As a secondary objective, the PICO Study will elucidate the cerebral (fMRI, neural activation during a n-back task; rsfMRI, functional connectivity at rest; DTI, white matter integrity; and ASL, cerebral blood flow) and neurometabolic mechanisms (cerebral Phe level) that accompany changes in Phe concentration. Cognition, and structural and functional parameters of the brain of adult patients with early-treated PKU will be cross-sectionally compared to healthy controls. All assessments will take place at the University Hospital Bern, Switzerland.RandomizationCentral randomization will be used to assign participants to the different treatment arms with age, sex, and center serving as the stratification factors. Randomization lists will be generated by an independent statistician.Blinding: All trial personnel other than the statistician generating the randomization list and the personnel at the facility preparing the interventional product are blinded to the assigned treatment.DiscussionUsing a combination of neuropsychological and neuroimaging data, the PICO Study will considerably contribute to improve the currently insufficient level of evidence on how adult patients with early-treated PKU should be managed.Trial registrationThe study is registered at clinicaltrials.gov (NCT03788343) on the 27th of December 2018, at kofam.ch (SNCTP000003117) on the 17th of December 2018, and on the International Clinical Trials Registry Platform of the WHO.
Databáze: OpenAIRE
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